T lymphocytes (T cells) recognize only a small number of segments (antigenic sites) of a foreign protein, and only when the segment is presented on the surface of an antigen presenting cell in association with a major histocompatibility (MHC) molecule. The initial phase of this project is to identify by statistical methods properties of the known antigenic sites that distinguish them from the rest of the protein. Because the available data is mostly for helper T cell sites, the study is limited to these, but some sites specific to cytotoxic T cells are becoming known and the methods developed will be applicable in the study of cytotoxic T cell and eventually antibody sites as well. These methods now include powerful matching techniques from statistical studies of human disease which can assess the significance of individual contributions to antigenicity while accounting for the cross- correlations between putative predictive parameters. Prediction of T-cell sites from the primary sequence will be important in the design of synthetic vaccines. We continue our study on intrinsic sequence features that are important for T-cell recognition, and pursue the question of MHC restriction. Our recent approach is to simulate the complex of antigen-class II molecule, based on the known structure of the class I molecule. By repeating the analysis for all the antigens that are restricted to a specific MHC, we look for consistent rules, and then test our hypothesis by simulating the same antigens with other MHC types for which they are known not to be restricted. (See also report ZO1 CB 04020-11 MET of Jay A. Berzofsky, who, together with Charles DeLisi, initiated many of the questions and with whom this work is closely coordinated.) This laboratory also collaborated with Attila Szabo and Noam Agmon (LCP, NIDDK) on the analysis of chemical reaction kinetics related to florescence quenching.